Molecular Design and Chemical Synthesis of Pharmaceutical-Ligands and Pharmaceutical-Pharmaceutical Analogs with Multiple Mechanisms of Action

摘要

Multi-phase and single-phase chemical reaction schemes have been developed for the synthesis of pharmaceutical-ligand analogs, pharmaceutical-pharmaceutical analogs, and similar molecular-molecular analogs that possess multiple mechanisms of action. The multi-phase organic chemical reaction schemes include relatively mild reaction conditions, high end product yields, and comparatively rapid completion of chemical reactions, which are all of particular utility for the synthesis of preparations including covalent pharmaceutical-receptor ligand or pharmaceutical-immunoglobulin analogs. Examples of pharmaceutical-ligand preparations that can be synthesized utilizing the multi-step chemical reaction schemes include covalent chemotherapeutic-ligand agents that possess selective targeted delivery properties and a capacity to exert additive and synergistic levels of cytotoxic anti-neoplastic potency. Pharmaceutical-pharmaceutical analogs, including chemotherapeutic-chemotherapeutic analogs that are capable of exerting multiple mechanisms of action, can be synthesized using either of the described multi-phase or single-phase organic chemistry reaction schemes. Each of these representative examples has utility against a spectrum of disease states including, for example, neoplastic conditions such as mammary adenocarcinoma/carcinoma, ovarian carcinoma, prostatic carcinoma, intestinal carcinoma, melanoma, leukemia, myeloma, and lymphoma.

主权项

1. A method of single- or multi-phase organic chemical reaction for the synthetic production of covalent pharmaceutical-receptor ligand, pharmaceutical-immunoglobulin, pharmaceutical-immunoglobulin fragment, pharmaceutical-synthetic ligand, multi pharmaceutical-pharmaceutical complex, pharmaceutical-molecule, and molecule-molecule analogs, and fragments thereof, that may possess selective targeted delivery properties for use in fighting specific diseases including cancer/neoplastic conditions, auto-immune disorders, and organ-transplant rejection in humans and animals in need thereof, the method comprising:
forming a reaction mixture by combining at least one covalent bond-forming reagent containing at least one amine-reactive chemical group (e.g. N-hydroxysuccinimide esters) in addition to at least one ultraviolet light activated diazirine chemical group, or at least one phosphate reactive group (e.g. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide with imidazole), or at least one carboxyl reactive group (e.g. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide with N-hydroxysuccinimide), or at least one hydroxyl reactive group, or at least one sulfhydryl reactive group, or at least one carbonyl reactive group, and optionally utilizing at least one reactive intermediate synthesized as a precursor in the reaction mixture.